tbuckley/cabot-search huggingface dataset:
The <i>MC1R</i> r allele does not increase melanoma risk in <i>MITF</i> E318K carriers
Authors: Courtney K Wallingford, Anastassia Demeshko, Asha Krishnankutty Krishnakripa, Darren J Smit, David L Duffy, Brigid Betz-Stablein, Annette Pflugfelder, Kasturee Jagirdar, Elizabeth Holland, Graham J Mann, Clare A Primiero, Tatiane  Yanes, Josep Malvehy, Cèlia Badenas, Cristina Carrera, Paula Aguilera, Catherine M   Olsen, Sarah V Ward, Nikolas K Haass, Richard A Sturm, Susana  Puig, David C   Whiteman, Matthew H Law, Anne E Cust, Miriam Potrony, H  Peter  Soyer, Aideen M McInerney-Leo
Journal: British Journal of Dermatology (2023)

Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored.To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K- individuals.Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/- cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank).The cohort comprised 1165 MITF E318K- and 322 E318K+ individuals. In E318K- cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P < 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P < 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67-2.49); P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54-1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20-1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P < 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals.RHC alleles/genotypes modify melanoma risk differently in MITF E318K- and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K- individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals.
Sucrase-isomaltase genotype and response to a starch-reduced and sucrose-reduced diet in IBS-D patients
Authors: Andreea Zamfir-Taranu, Britt-Sabina Löscher, Diab M. Husein, Abdullah Hoter, Koldo Garcia-Etxebarria, Usune Etxeberria, Lucía Gayoso, Gabriele Mayr, Clara Nilholm, Rita J. Gustafsson, Oliver Ozaydin, Tenghao Zheng, Cristina Esteban-Blanco, Isotta Bozzarelli, Ferdinando Bonfiglio, Sandra Rizk, Andre Franke, Luis Bujanda, Hassan Y. Naim, Bodil Ohlsson, Mauro D'Amato
Journal: Gut (2023)
After a Night of Odd Angles
Authors: Naomi Dean
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Morphology-guided transcriptomic analysis of human pancreatic cancer organoids reveals microenvironmental signals that enhance invasion
Authors: Yea Ji Jeong, Hildur Knutsdottir, Fatemeh Shojaeian, Michael G. Lerner, Maria F. Wissler, Elodie Henriet, Tammy Ng, Shalini Datta, Bernat Navarro-Serer, Peter Chianchiano, Benedict Kinny-Köster, Jacquelyn W. Zimmerman, Genevieve Stein-O’Brien, Matthias M. Gaida, James R. Eshleman, Ming-Tseh Lin, Elana J. Fertig, Andrew J. Ewald, Joel S. Bader, Laura D. Wood
Journal: Journal of Clinical Investigation (2023)

Pancreatic ductal adenocarcinoma (PDAC) frequently presents with metastasis, but the molecular programs in human PDAC cells that drive invasion are not well understood. Using an experimental pipeline enabling PDAC organoid isolation and collection based on invasive phenotype, we assessed the transcriptomic programs associated with invasion in our organoid model. We identified differentially expressed genes in invasive organoids compared with matched noninvasive organoids from the same patients, and we confirmed that the encoded proteins were enhanced in organoid invasive protrusions. We identified 3 distinct transcriptomic groups in invasive organoids, 2 of which correlated directly with the morphological invasion patterns and were characterized by distinct upregulated pathways. Leveraging publicly available single-cell RNA-sequencing data, we mapped our transcriptomic groups onto human PDAC tissue samples, highlighting differences in the tumor microenvironment between transcriptomic groups and suggesting that non-neoplastic cells in the tumor microenvironment can modulate tumor cell invasion. To further address this possibility, we performed computational ligand-receptor analysis and validated the impact of multiple ligands (TGF-β1, IL-6, CXCL12, MMP9) on invasion and gene expression in an independent cohort of fresh human PDAC organoids. Our results identify molecular programs driving morphologically defined invasion patterns and highlight the tumor microenvironment as a potential modulator of these programs.
Cutaneous features at injection sites of intravenous mephedrone
Authors: Manuel Agud de Dios, Jorge Arroyo-Andres, Carmen Rubio-Muniz, Maria Concepcion Garrido, Eloy Tarin-Vicente
Journal: British Journal of Dermatology (2023)

We present the cutaneous adverse effects of subcutaneous extravasation of mephedrone resulting in thrombotic vasculopathy and chronic ulcerations. Due to the increasing use of mephedrone, especially among the community of men who have sex with men, general physicians and dermatologists should be familiarized with these possible events.
Still Looking for a Simple, Effective Prevention Measure for Neonatal Sepsis in High-Mortality Settings
Authors: Stephanie J. Schrag, Cynthia G. Whitney
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
2-[18F]FDG PET/CT Flare-up Phenomena Following T-Cell Engager Bispecific Antibody in Multiple Myeloma
Authors: Bastien Jamet, Caroline Bodet-Milin, Philippe Moreau, Françoise Kraeber-Bodéré, Cyrille Touzeau
Journal: Clinical Nuclear Medicine (2023)

T-cell-redirecting bispecific antibodies represent a new standard of care for the treatment of triple-class refractory myeloma patients. Here, 2-[ 18 F]FDG PET/CT imaging was performed on a 61-year-old woman with relapsed myeloma to determine metabolic response to talquetamab, a GPRC5DxCD3-bispecific antibody. At day 28, monoclonal (M) component assessment confirmed very good partial response (97% monoclonal protein reduction), whereas 2-[ 18 F]FDG PET/CT imaging revealed early bone flare-up phenomena. At day 84, bone marrow aspirate, M-component assessment, and 2-[ 18 F]FDG PET/CT demonstrated complete response, confirming the early flare-up hypothesis.
Uncommon Manifestation of Oligometastatic Prostate Cancer
Authors: Cibele Luna, Oleksandr N. Kryvenko, Jose Martinez, Rakesh Singal, Russ Kuker
Journal: Clinical Nuclear Medicine (2023)

Abstract A 76-year-old man with a history of prostate cancer diagnosed in 2008 developed biochemical recurrence in 2010 and started intermittent androgen deprivation therapy. In 2021, due to rising prostate-specific antigen, an 18 F-piflufolastat PSMA PET/CT was performed. It showed a radiotracer-avid sclerotic lesion in the right iliac bone and an indeterminate radiotracer-avid nodule in the umbilical region, demonstrating progressive enlargement and increased uptake on subsequent imaging. Pathologic analysis of the umbilical nodule revealed metastatic prostate cancer—a finding eponymically referred to as a Sister Mary Joseph nodule.
The Status of Epidemic Encephalitis as an Independent Disease
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association between physical activity and the time course of cancer recurrence in stage III colon cancer
Authors: Justin C Brown, Chao Ma, Qian Shi, Donna Niedzwiecki, Tyler Zemla, Felix Couture, Philip Kuebler, Pankaj Kumar, Judith O Hopkins, Benjamin Tan, Smitha Krishnamurthi, Eileen M O'Reilly, Anthony F Shields, Jeffrey A Meyerhardt
Journal: British Journal of Sports Medicine (2023)

Objective We determined if postoperative physical activity prevents or delays cancer recurrence in patients with stage III colon cancer. Methods This cohort study nested within a randomised trial enrolled 1696 patients with surgically resected stage III colon cancer. Physical activity was calculated based on self-reporting during and after chemotherapy. Patients were classified as physically active (≥9 MET-h/wk, comparable with the energy expenditure of 150 min/wk of brisk walking, consistent with the current physical activity guidelines for cancer survivors) or physically inactive (&lt;9 MET-h/wk). The confounder-adjusted hazard rate (risk of recurrence or death) and HR by physical activity category were estimated with continuous time to allow non-proportionality of hazards. Results During a median 5.9 years follow-up, 457 patients experienced disease recurrence or death. For physically active and physically inactive patients, the risk of disease recurrence peaked between 1 and 2 years postoperatively and declined gradually to year 5. The risk of recurrence in physically active patients never exceeded that of physically inactive patients during follow-up, suggesting that physical activity prevents—as opposed to delays—cancer recurrence in some patients. A statistically significant disease-free survival benefit associated with physical activity was observed during the first postoperative year (HR 0.68, 95% CI 0.51 to 0.92). A statistically significant overall survival benefit associated with physical activity was observed during the first three postoperative years (HR 0.32, 95% CI 0.19 to 0.51). Conclusions In this observational study of patients with stage III colon cancer, postoperative physical activity is associated with improved disease-free survival by lowering the recurrence rate within the first year of treatment, which translates into an overall survival benefit.
Photocrosslinkable, Injectable Locust Bean Gum Hydrogel Induces Chondrogenic Differentiation of Stem Cells for Cartilage Regeneration
Authors: Yangyang Qu, Si He, Shixing Luo, Jinmin Zhao, Ruiming Liang, Chuanan Liao, Li Zheng
Journal: Advanced Healthcare Materials (2023)

Due to the limited therapeutic efficacy of current treatments, articular cartilage regeneration is still challenging work. Scaffold-based tissue engineering provides a promising strategy for cartilage regeneration, but most scaffolds are limited by poor mechanical properties or unfavorable biocompatibility. Here, a novel photocrosslinkable, injectable locust bean gum (LBG)-methacrylate (MA) hydrogel is reported as a biomimetic extracellular matrix (ECM) for cartilage repair with minimal invasive operation. LBG-MA hydrogels show controllable degradation rate and improve mechanical properties and excellent biocompatibility. More importantly, LBG-MA hydrogel significantly induces bone mesenchymal stem cells to chondrogenic differentiation in vitro, as evidenced by high accumulation of cartilage-specific ECM components glycosaminoglycan and upregulated expression of key chondrogenic genes (collagen type II, aggrecan, and sex determining region Y-box9). Besides, the hydrogel is injectable, which can be in situ crosslinked via UV irradiation. Further, the photocrosslinkable hydrogels accelerate cartilage healing in vivo after 8 weeks of therapy. A strategy is provided here for photocrosslinkable, injectable, biodegradable scaffold fabrication based on native polysaccharide polymer for minimal invasive cartilage repair.
Health Equity and Measures Hospital Rankings—Reply
Authors: Tavia Binger, Ben Harder
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Unintended Pregnancy and Maternal and Infant Health Outcomes
Authors: Minjing Luo, Qianyun Chai, Yutong Fei
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hydrogel-forming microarray patches with solid dispersion reservoirs for transdermal long-acting microdepot delivery of a hydrophobic drug
Authors: Yara A. Naser, Ismaiel A. Tekko, Lalitkumar K. Vora, Ke Peng, Qonita K. Anjani, Brett Greer, Christopher Elliott, Helen O. McCarthy, Ryan F. Donnelly
Journal: Journal of Controlled Release (2023)

Hydrogel-forming microarray patches (HF-MAPs) are used to circumvent the skin barrier and facilitate the noninvasive transdermal delivery of many hydrophilic substances. However, their use in the delivery of hydrophobic agents is a challenging task. This work demonstrates, for the first time, the successful transdermal long-acting delivery of the hydrophobic atorvastatin (ATR) via HF-MAPs using poly(ethylene)glycol (PEG)-based solid dispersion (SD) reservoirs. PEG-based SDs of ATR were able to completely dissolve within 90 s in vitro. Ex vivo results showed that 2.05 ± 0.23 mg of ATR/0.5 cm2 patch was delivered to the receiver compartment of Franz cells after 24 h. The in vivo study, conducted using Sprague Dawley rats, proved the versatility of HF-MAPs in delivering and maintaining therapeutically-relevant concentrations (> 20 ng·mL-1) of ATR over 14 days, following a single HF-MAP application for 24 h. The long-acting delivery of ATR suggests the successful formation of hydrophobic microdepots within the skin, allowing for the subsequent sustained delivery as they gradually dissolve over time, as shown in this work. When compared to the oral group, the use of the HF-MAP formulation improved the overall pharmacokinetics profile of ATR in plasma, where significantly higher AUC values resulting in ∼10-fold higher systemic exposure levels were obtained. This novel system offers a promising, minimally-invasive, long-acting alternative delivery system for ATR that is capable of enhancing patient compliance and therapeutic outcomes. It also proposes a unique promising platform for the long-acting transdermal delivery of other hydrophobic agents.
Internal consistency reliability of mental health questionnaires in college student athletes
Authors: Daniel J Taylor, Alisa Huskey, Kelly N Kim, Sarah E Emert, Sophie Wardle-Pinkston, Alex Auerbach, John M Ruiz, Michael A Grandner, Rachel Webb, Michelle Skog, Thomas Milord
Journal: British Journal of Sports Medicine (2023)

To examine the internal consistency reliability and measurement invariance of a questionnaire battery designed to identify college student athletes at risk for mental health symptoms and disorders.College student athletes (N=993) completed questionnaires assessing 13 mental health domains: strain, anxiety, depression, suicide and self-harm ideation, sleep, alcohol use, drug use, eating disorders, attention deficit hyperactivity disorder (ADHD), bipolar disorder, post-traumatic stress disorder (PTSD), gambling and psychosis. Internal consistency reliability of each measure was assessed and compared between sexes as well as to previous results in elite athletes. Discriminative ability analyses were used to examine how well the cut-off score on the strain measure (Athlete Psychological Strain Questionnaire) predicted cut-offs on other screening questionnaires.Strain, anxiety, depression, suicide and self-harm ideation, ADHD, PTSD and bipolar questionnaires all had acceptable or better internal consistency reliability. Sleep, gambling and psychosis questionnaires had questionable internal consistency reliability, although approaching acceptable for certain sex by measure values. The athlete disordered eating measure (Brief Eating Disorder in Athletes Questionnaire) had poor internal consistency reliability in males and questionable internal consistency reliability in females.The recommended mental health questionnaires were generally reliable for use with college student athletes. To truly determine the validity of the cut-off scores on these self-report questionnaires, future studies need to compare the questionnaires to a structured clinical interview to determine the discriminative abilities.
Raft of US state laws restrict access to treatments for gender dysphoria
Authors: Jennifer Block
Journal: BMJ (2023)

Raft of US state laws restrict access to treatments for gender dysphoria Jennifer BlockTennessee has joined a growing list of US states that have passed laws restricting physicians from administering what are known as "gender affirming" treatments to minors.The laws prohibit the prescribing of drugs to suppress puberty, such as gonadotrophin releasing hormone analogueues and cross-sex hormones, in patients under 18 as well as all related surgeries for the purposes of treating gender dysphoria.